The overall goal of the Alzheimer's Disease Research Center (ADRC) at Johns Hopkins University (JHU) is to facilitate research in Alzheimer's disease (AD) and related disorders throughout the research community at JHU and associated institutions. The ADRC is comprised of four Cores: a Clinical Core , a Data Management and Statistics Core, a Neuropathology Core, and an Education Core. The cores will work together to provide the infrastructure and resources to the JHU community so that clinical and basic research in AD and related disorders can continue to flourish and expand. In addition, three projects are proposed. The first Project pertains to executive function impairments in subjects with Mild Cognitive Impairment (MCI) and their relation to progression of cognitive decline over time. The second Project pertains to the clinical-pathological-biochemical alterations present in the earliest stage of pathology in the perforant pathway of the medial temporal lobe among individuals who have come to autopsy, and are either normal, meet criteria for MCI, or have mild AD. The third Project will examine neuropathological, neurochemical, and biochemical aspects of synaptic pathology occurring in several lines of behaviorally-characterized transgenic mice. Cooperative studies with investigators at other ADCs and related research institutions will continue to be conducted, including multi-center clinical trials. Data sharing with other investigators in the AD research community will continue through regular submissions to the National Alzheimer Disease Coordinating Center (NACC).